Dataset Information

Dysregulated mitochondrial metabolism upon cigarette smoke exposure in various human bronchial epithelial cell models.

ABSTRACT: Exposure to cigarette smoke (CS) is the primary risk factor for developing chronic obstructive pulmonary disease. The impact of CS exposure on the molecular mechanisms involved in mitochondrial quality control in airway epithelial cells is incompletely understood. Undifferentiated or differentiated primary bronchial epithelial cells were acutely/chronically exposed to whole CS (WCS) or CS extract (CSE) in submerged or air-liquid interface conditions. Abundance of key regulators controlling mitochondrial biogenesis, mitophagy and mitochondrial dynamics was assessed. Acute exposure to WCS or CSE increased the abundance of components of autophagy and receptor-mediated mitophagy in all models. Although mitochondrial content and dynamics appeared to be unaltered in response to CS, changes in both the molecular control of mitochondrial biogenesis and a shift toward an increased glycolytic metabolism were observed in particular in differentiated cultures. These alterations persisted, at least in part, after chronic exposure to WCS during differentiation and upon subsequent discontinuation of WCS exposure. In conclusion, smoke exposure alters the regulation of mitochondrial metabolism in airway epithelial cells, but observed alterations may differ between various culture models used. This article has an associated First Person interview with the joint first authors of the paper.

SUBMITTER: Tulen CBM

PROVIDER: S-EPMC8990921 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dysregulated mitochondrial metabolism upon cigarette smoke exposure in various human bronchial epithelial cell models.

Tulen Christy B M CBM Wang Ying Y Beentjes Daan D Jessen Phyllis J J PJJ Ninaber Dennis K DK Reynaert Niki L NL van Schooten Frederik-Jan FJ Opperhuizen Antoon A Hiemstra Pieter S PS Remels Alexander H V AHV

Disease models & mechanisms 20220328 3

Exposure to cigarette smoke (CS) is the primary risk factor for developing chronic obstructive pulmonary disease. The impact of CS exposure on the molecular mechanisms involved in mitochondrial quality control in airway epithelial cells is incompletely understood. Undifferentiated or differentiated primary bronchial epithelial cells were acutely/chronically exposed to whole CS (WCS) or CS extract (CSE) in submerged or air-liquid interface conditions. Abundance of key regulators controlling mitoc ...[more]

PMID: 35344036

Similar Datasets

Project description:BackgroundChronic Obstructive Pulmonary Disease (COPD) is a progressive lung disease characterized by chronic inflammation upon inhalation of noxious particles, e.g., cigarette smoke. FAM13A is one of the genes often found to be associated with COPD, however its function in the pathophysiology of COPD is incompletely understood. We studied its role in airway epithelial barrier integrity and cigarette smoke-induced epithelial responses.Materials and methodsProtein level and localization of FAM13A was assessed with immunohistochemistry in lung tissue from COPD patients and non-COPD controls. In vitro, FAM13A expression was determined in the absence or presence of cigarette smoke extract (CSE) in primary airway epithelial cells (AECs) from COPD patients and controls by western blotting. FAM13A was overexpressed in cell line 16HBE14o- and its effect on barrier function was monitored real-time by electrical resistance. Expression of junctional protein E-cadherin and β-catenin was assessed by western blotting. The secretion of neutrophil attractant CXCL8 upon CSE exposure was measured by ELISA.ResultsFAM13A was strongly expressed in airway epithelium, but significantly weaker in airways of COPD patients compared to non-COPD controls. In COPD-derived AECs, but not those of controls, FAM13A was significantly downregulated by CSE. 16HBE14o- cells overexpressing FAM13A built up epithelial resistance significantly more rapidly, which was accompanied by higher E-cadherin expression and reduced CSE-induced CXCL8 levels.ConclusionOur data indicate that the expression of FAM13A is lower in airway epithelium of COPD patients compared to non-COPD controls. In addition, cigarette smoking selectively downregulates airway epithelial expression of FAM13A in COPD patients. This may have important consequences for the pathophysiology of COPD, as the more rapid build-up of epithelial resistance upon FAM13A overexpression suggests improved (re)constitution of barrier function. The reduced epithelial secretion of CXCL8 upon CSE-induced damage suggests that lower FAM13A expression upon cigarette smoking may facilitate epithelial-driven neutrophilia.

Dataset Information

Dysregulated mitochondrial metabolism upon cigarette smoke exposure in various human bronchial epithelial cell models.

Publications

Dysregulated mitochondrial metabolism upon cigarette smoke exposure in various human bronchial epithelial cell models.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets